DESCRIPTION, OVERALL (provided by applicant): The development of transgenic technology and gene targeting protocols has resulted in numerous mouse lines with specific phenotypes and well-defined DNA structural changes. Candidate genes involved in kidney development and/or disease have been identified and transgenic mice are being generated using this technology. In addition, new targets of kidney disease are being identified and potential therapeutic interventions developed. The Vanderbilt O'Brien Center was funded for 20 continuous years as a P50 grant to study the "Biology of Progressive Nephron Destruction". With the redirection of the O'Brien Centers to P30 Center Cores, we now propose to serve as a national resource by developing the O'Brien Mouse Kidney Physiology and Disease Core (MKPDC). This Center represents a close interaction between researchers at Vanderbilt and the University of Utah. The mission of the MKPDC is to advance medical and biological research by providing the scientific community with standardized, high quality phenotyping services for mouse models of kidney disease and to provide experimental platforms to test potential therapeutic interventions. MKPDC will provide an extended research base that will enhance the efficiency of medical and biological research using mouse models of kidney disease. By broadening the availability of sophisticated in vivo phenotyping tests, we aim to help investigators identify and characterize new mouse models of kidney disease and potential interventions and therapies. The MKPDC consists of 4 different, yet interlinked Biomedical Cores, including. 1) the Phenotyping and Pathophysiology Core that will provide a) mouse kidney phenotyping resources to the Vanderbilt and Utah research communities and to interested researchers at other institutions;and b) a range of mouse models of kidney disease that will be available for testing potential therapeutics;2) the Histology and Morphornetry Core for routine and specialized renal histologic and quantitative analyses: 3) the In Vivo Imaging Core that will provide established and novel in vivo imaging modalities to study mouse kidney physiology and pathophysiology;and 4) the Renal Cre Transgenic Core to develop kidney segment specific and inducible Cre mice for selective gene deletion. In addition, the Biomedical Cores have as a major goal the development and testing of new technology and/or mouse models for the study of kidney disease. Moreover, as a major goal of the MKPDC is to serve as an educational resource, an Education Core will serve as a national resource of information and training for research communities interested in mouse models of kidney disease. An Administrative Component and a Pilot and Feasibility Program complete the MKPDC Center. NIH support for the MKPDC is greatly amplified by a diverse and complementary array of research core services at Vanderbilt and the University of Utah.